Mutation in ROBO 3 Gene in Patients with Horizontal Gaze Palsy with Progressive Scoliosis Syndrome: A Systematic Review

Int J Environ Res Public Health. 2020 Jun 22;17(12):4467. doi: 10.3390/ijerph17124467.


Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movements with progressive scoliosis developing in childhood and adolescence. Mutations in the Roundabout (ROBO3) gene located on chromosome 11q23-25 are responsible for the development of horizontal gaze palsy and progressive scoliosis. However, some studies redefined the locus responsible for this pathology to a 9-cM region. This study carried out a systematic review in which 25 documents were analyzed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was made in the following electronic databases from January 1995 to October 2019: PubMed, Scopus, Web of Science, PEDRO, SPORT Discus, and CINAHL. HGPPS requires a multidisciplinary diagnostic approach, in which magnetic resonance imaging might be the first technique to suggest the diagnosis, which should be verified by an analysis of the ROBO3 gene. This is important to allow for adequate ocular follow up, apply supportive therapies to prevent the rapid progression of scoliosis, and lead to appropriate genetic counseling.

Keywords: children; familial horizontal; gaze palsy; mutation; scoliosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Child
  • Female
  • Humans
  • Male
  • Mutation
  • Ocular Motility Disorders*
  • Ophthalmoplegia, Chronic Progressive External* / genetics
  • Receptors, Cell Surface* / genetics
  • Receptors, Immunologic
  • Scoliosis* / genetics


  • ROBO3 protein, human
  • Receptors, Cell Surface
  • Receptors, Immunologic

Supplementary concepts

  • Gaze Palsy, Familial Horizontal, with Progressive Scoliosis